Impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen metabolism.
Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early wound healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target.
Kirfel
Jutta
J
Institute of Pathology, University Hospital Medical School, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany. Jutta.Kirfel@ukb.uni-bonn.de
Pantelis
Dimitrios
D
Kabba
Mustapha
M
Kahl
Philip
P
Röper
Anke
A
Kalff
Jörg C
JC
Buettner
Reinhard
R
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D007410:Intestinal Diseases / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000293:injuries*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics*; D033081:Shear Strength; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics*
D024061:Collagen Type III; C491382:Fhl2 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D003094:Collagen